The effects of the cryoprotective agents: dimethyl sulfoxide, glycerol, ethylene glycol, as well as of freezing and thawing on the rate of gene mutation in the eight-cell mouse embryo will be investigated. Embryos of the BALB/cBy inbred strain will be treated in vitro with a cryoprotective agent and reimplanted or frozen in liquid nitrogen and thawed and then reimplanted. The liveborn, when mature, will be mated to an untreated mouse of the same strain. The progeny will be crossed back to the treated parent to obtain test mice, which if homozygous, could reveal recessive mutations. In order to optimize the number of genes easily screened for mutation, two large sets of genes have been chosen: the set that determines histocompatibility antigens (screened by tailskin graft exchanges) and the set that determines morphogenesis (screened by multivariate analysis of bone measurements).